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1
Wirth, Manfred P., and Oliver W. Hakenberg. "Curative Treatment of Prostate Cancer." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133890.
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The guidelines for the curative treatment of prostate cancer presented by the German Society of Urology are discussed. They are based on the current knowledge of the outcomes of surgical and radiotherapeutic treatment for prostate cancer. Radical prostatectomy is recommended as the first-line treatment for organ-confined prostate cancer in patients with an individual life expectancy of at least 10 years. Radiotherapy can be considered as an alternative treatment modality, although current knowledge does not allow a definite assessment of the relative value of radiotherapy compared to radical prostatectomy. Locally advanced cT3 prostate cancer is overstaged in about 20% and curative treatment is possible in selected cases. Guidelines represent rules based on the available evidence. This implies that exceptions must be made whenever appropriate and that guidelines have to be reviewed regularly as new information becomes availableDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
2
Wirth, Manfred P., and Oliver W. Hakenberg. "Curative Treatment of Prostate Cancer." Karger, 1999. https://tud.qucosa.de/id/qucosa%3A27546.
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The guidelines for the curative treatment of prostate cancer presented by the German Society of Urology are discussed. They are based on the current knowledge of the outcomes of surgical and radiotherapeutic treatment for prostate cancer. Radical prostatectomy is recommended as the first-line treatment for organ-confined prostate cancer in patients with an individual life expectancy of at least 10 years. Radiotherapy can be considered as an alternative treatment modality, although current knowledge does not allow a definite assessment of the relative value of radiotherapy compared to radical prostatectomy. Locally advanced cT3 prostate cancer is overstaged in about 20% and curative treatment is possible in selected cases. Guidelines represent rules based on the available evidence. This implies that exceptions must be made whenever appropriate and that guidelines have to be reviewed regularly as new information becomes available.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
3
Wirth, Manfred P., and Michael Fröhner. "Adjuvant Hormonal Treatment for Prostate Cancer: The Bicalutamide Early Prostate Cancer Program." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133551.
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Adjuvant hormonal therapy has been demonstrated to be able to delay disease progression in nonmetastatic prostate cancer. To date, however, a favorable impact on survival has only been demonstrated in lymph-node-positive disease and in external-beam radiotherapy series with locally advanced and probably mainly micrometastatic tumors. The Bicalutamide Early Prostate Cancer Program is the largest study under way to define the role of adjuvant treatment in early prostate cancer and identify subgroups of patients likely to benefit from immediate hormonal therapy. At the time of the most recently published analysis, the risk of objective clinical progression was significantly reduced in the bicalutamide arm (hazards ratio 0.58, 95% confidence interval 0.51–0.66, p < 0.0001). However, further maturation of data is needed to see whether this difference will lead to a survival advantageDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
4
Wirth, Manfred P., and Michael Fröhner. "Adjuvant Hormonal Treatment for Prostate Cancer: The Bicalutamide Early Prostate Cancer Program." Karger, 2003. https://tud.qucosa.de/id/qucosa%3A27515.
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Adjuvant hormonal therapy has been demonstrated to be able to delay disease progression in nonmetastatic prostate cancer. To date, however, a favorable impact on survival has only been demonstrated in lymph-node-positive disease and in external-beam radiotherapy series with locally advanced and probably mainly micrometastatic tumors. The Bicalutamide Early Prostate Cancer Program is the largest study under way to define the role of adjuvant treatment in early prostate cancer and identify subgroups of patients likely to benefit from immediate hormonal therapy. At the time of the most recently published analysis, the risk of objective clinical progression was significantly reduced in the bicalutamide arm (hazards ratio 0.58, 95% confidence interval 0.51–0.66, p < 0.0001). However, further maturation of data is needed to see whether this difference will lead to a survival advantage.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
5
Knight, Kellie Ann. "Daily Image Guided Radiation Therapy for Prostate Cancer: An assessment of treatment plan reproducibility." Thesis, The University of Sydney, 2006. http://hdl.handle.net/2123/1628.
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It is well documented that for prostate cancer patients undergoing radiation therapy there is a correlation between target volume displacement and changes in bladder and rectal volumes. However, these studies have used a methodology that has captured only a subset of all treatment positions. This research used daily Computer Tomography (CT) imaging to comprehensively assess organ volumes, organ motion and their effect on dose, something that has never been performed previously, thus adding considerably to the understanding of the topic. Daily CT images were obtained using a Siemens Primus Linear Accelerator equipped with an in-room Somatom CT unit in the accelerator suite, marketed as ‘Primatom’, to accurately position the patient prior to treatment delivery. The internal structures of interest were contoured on the planning workstation by the investigator. The daily volume and location of the organs were derived from the computer to assess and analyse internal organ motion. The planned dose distribution was then imported onto the treatment CT datasets and used to compare the planned dose to i) the actual isocentre, where the isocentre was actually placed for that fraction, ii) the uncorrected isocentre, by un-doing any on-line corrections performed by the treatment staff prior to treatment delivery, and iii) the future isocentre, by placing the isocentre relative to internal organ motion on a daily basis. The results of this study did not confirm a statistically significant decrease in rectum volumes over time (hypothesis 1), however large fluctuations in bladder volume were confirmed (hypothesis 2). Internal organ motion for the rectum and bladder was demonstrated to be related to organ filling. Ideal planning volumes for these organs have been reported to minimise systematic and random uncertainty in the treatment volumes. An observed decrease in prostate volume over time, a systematic uncertainty in the location of the prostate at the time of the planning CT scan and a significant relationship between prostate centre of volume and rectum and bladder volumes has resulted in a recommendation that patients should be re-scanned during treatment to ensure appropriate clinical target volume coverage. A significant relationship between rectal and bladder volumes and the dose delivered to these organs was found (hypothesis 3). The dose delivered to the planning target volume was not related to the rectal or bladder volumes, although it was related to the motion of these organs. Despite these results only minimal effects on the dose delivered to any of the three isocentres occurred, indicating that the planned dose was accurately delivered using the methodology presented here (hypothesis 4). However the results do indicate that the patient preparation instructions need to be improved if margins are to be reduced in the future. It is unrealistic to assume that Image Guided Radiation Therapy will ever become routine practice due to infrastructure costs and time limitations. This research will inform radiation therapy centres of the variables associated with prostate cancer treatment on a daily basis, something that has never before been realistically achievable. As a result centres will be able to devise protocols to improve treatment outcomes.
6
Knight, Kellie Ann. "Daily Image Guided Radiation Therapy for Prostate Cancer: An assessment of treatment plan reproducibility." University of Sydney, 2006. http://hdl.handle.net/2123/1628.
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Doctor of Health ScienceIt is well documented that for prostate cancer patients undergoing radiation therapy there is a correlation between target volume displacement and changes in bladder and rectal volumes. However, these studies have used a methodology that has captured only a subset of all treatment positions. This research used daily Computer Tomography (CT) imaging to comprehensively assess organ volumes, organ motion and their effect on dose, something that has never been performed previously, thus adding considerably to the understanding of the topic. Daily CT images were obtained using a Siemens Primus Linear Accelerator equipped with an in-room Somatom CT unit in the accelerator suite, marketed as ‘Primatom’, to accurately position the patient prior to treatment delivery. The internal structures of interest were contoured on the planning workstation by the investigator. The daily volume and location of the organs were derived from the computer to assess and analyse internal organ motion. The planned dose distribution was then imported onto the treatment CT datasets and used to compare the planned dose to i) the actual isocentre, where the isocentre was actually placed for that fraction, ii) the uncorrected isocentre, by un-doing any on-line corrections performed by the treatment staff prior to treatment delivery, and iii) the future isocentre, by placing the isocentre relative to internal organ motion on a daily basis. The results of this study did not confirm a statistically significant decrease in rectum volumes over time (hypothesis 1), however large fluctuations in bladder volume were confirmed (hypothesis 2). Internal organ motion for the rectum and bladder was demonstrated to be related to organ filling. Ideal planning volumes for these organs have been reported to minimise systematic and random uncertainty in the treatment volumes. An observed decrease in prostate volume over time, a systematic uncertainty in the location of the prostate at the time of the planning CT scan and a significant relationship between prostate centre of volume and rectum and bladder volumes has resulted in a recommendation that patients should be re-scanned during treatment to ensure appropriate clinical target volume coverage. A significant relationship between rectal and bladder volumes and the dose delivered to these organs was found (hypothesis 3). The dose delivered to the planning target volume was not related to the rectal or bladder volumes, although it was related to the motion of these organs. Despite these results only minimal effects on the dose delivered to any of the three isocentres occurred, indicating that the planned dose was accurately delivered using the methodology presented here (hypothesis 4). However the results do indicate that the patient preparation instructions need to be improved if margins are to be reduced in the future. It is unrealistic to assume that Image Guided Radiation Therapy will ever become routine practice due to infrastructure costs and time limitations. This research will inform radiation therapy centres of the variables associated with prostate cancer treatment on a daily basis, something that has never before been realistically achievable. As a result centres will be able to devise protocols to improve treatment outcomes.
7
Wirth, Manfred P., and Michael Fröhner. "Perspectives in Adjuvant Treatment of Prostate Cancer." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133839.
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Wirth, Manfred P., and Michael Fröhner. "Perspectives in Adjuvant Treatment of Prostate Cancer." Karger, 2002. https://tud.qucosa.de/id/qucosa%3A27540.
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Elshafae, Said Mohammed Abbas. "Pathogenesis and Treatment of Canine Prostate Cancer." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1492081831172341.
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Martinez, De Pinillos Bayona A. "Light-based therapies in prostate cancer treatment." Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1532467/.
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Photodynamic Therapy (PDT) and Photochemical Internalisation (PCI) are both light-based therapies which can be used for the focal treatment of cancer. Both PDT and PCI require the combination of photosensitisers, light and molecular oxygen to induce photooxidative reactions that damage biomolecules. However, while PDT employs a photosensitiser as the sole therapeutic agent, PCI combines low-dose PDT with another therapeutic agent to enable the improved delivery of this agent to its intended subcellular targets. The overall aim of this study was to investigate PDT and PCI for prostate cancer in both in vitro and in vivo tumour models. In the PCI procedures, the ribosome inactivating protein type 1 saporin was used as a model chemotherapy agent. We have concluded an enhancement in cell killing in prostate carcinoma cells after PCI compared to PDT in 2-dimensional models, i.e. 80% cell death, compared to 32% killing after PDT. Similar observations resulted from qualitative observations in the 3-dimensional model. Moreover, conjugation of a photosensitiser to cell penetrating peptides (TAT or Antp), resulted in a similar difference in cytotoxicity after PCI and PDT using lower concentrations of the conjugates - 76% and 14% respectively. These data confirm the synergistic effect of drug and photosensitiser in PCI. Three different clinically relevant photosensitisers were used in vivo in a subcutaneous rat model. Vascular-targeted PDT resulted in the most efficient treatment, and photosensitisers targeting a cellular effect, showed a better outcome with shorter drug-light intervals. The analysis of tumour samples through immunohistochemistry and molecular analysis revealed an innate inflammatory response that led to an adaptive immune response. A highly suppressive tumour microenvironment was suggested by the infiltration of regulatory T cells (FoxP3+), up-regulation of PD-L1 and down-regulation of cytolytic proteins (i.e. Perforin). Moreover, the beneficial effect of using immunoadjuvants (cyclophosphamide) was investigated. Light based therapies could play an important role in prostate cancer treatment both eradicating tumours and generating long-term immune protection against secondary tumour deposits.
11
Fridriksson, Jon Örn. "Adverse effects of curative treatment of prostate cancer." Doctoral thesis, Umeå universitet, Urologi och andrologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-128709.
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Background Screening for prostate cancer is debated, there is conflicting data on the net benefit of screening. Men who consider screening need to be informed on the pros and cons. Rehospitalization after surgery can be used as an indicator of general quality of care. For radical prostatectomy, little is known on the readmission rate after surgery. Men diagnosed with low- and intermediate-risk prostate cancer have low prostate-cancer specific mortality. However, adverse effects after curative treatment can be severe and decrease quality of life. Curative treatments for prostate cancer differ mainly in the pattern of adverse effects but detailed analysis of long-term adverse effects is lacking. The aim of this thesis was to assess the perioperative quality of radical prostatectomy and the risk of adverse effects after curative treatment for prostate cancer. Material and Methods In this thesis, data from the National Prostate Cancer Register (NPCR) and other nationwide Swedish registers were used. By use of the Swedish personal identity number, NPCR was cross-linked to other registers creating Prostate Cancer data Base Sweden (PCBaSe), a large dataset for research. Results The proportion of men who had received information on the pros and cons of screening for prostate cancer with PSA testing was low (14%) indicating that the majority of men who were screened did not make an informed decision. The risk of rehospitalization within 90 days after radical prostatectomy was approximately 10% and similar after retropubic and robot-assisted radical prostatectomy. Compared to controls, there was an increased risk of adverse effects after both radiotherapy and radical prostatectomy up to twelve years after treatment and the overall risk was quite similar after retropubic and robot-assisted radical prostatectomy. Conclusion Improved information to men on the pros and cons of PSA screening is warranted. The risk of adverse effects was elevated up to 12 years after curative treatment for prostate cancer. The pattern of adverse effects was different after radiotherapy and radical prostatectomy but quite similar after retropubic and robot-assisted radical prostatectomy.
12
Ünlü, Ali. "Mechanism of invasion by prostate cancer." Thesis, University of Glasgow, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244438.
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Ladjevardi, Sam. "Imaging and Treatment Outcome of Potentially Curable Prostate Cancer." Doctoral thesis, Uppsala universitet, Urologkirurgi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-171754.
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The over-all aim of the present study was to compare the results of treatment with curative intent, with conservative treatment in men with prostate cancer (PCa) without distant metastases. In a population-based cohort in Sweden, the predictive value of prostate-specific antigen (PSA) was evaluated and the relative survival of men considered plausible candidates for treatment with curative intent was investigated. We also evaluated the association between curative treatment and cause-specific mortality, and over-all as well as relative survival in men diagnosed with PCa with a serum PSA level between 20 and 100 ng/ml. Due to the uncertainly of transrectal ultrasound-guided biopsy in the diagnosis of PCa, we created a model for prostate imaging to increase the safety of guided Core Needle Biopsy (CNB) in men with suspect PCa, thereby improving staging. Material and methods. The cohorts in the first three studies were prospectively included in a population-based register (the National Prostate Cancer Register). Study IV was a clinical study on patients included between 2010 and 2011. Results. Regardless of Gleason Score, a positive relationship between survival and serum PSA level categories in patients with a PSA level> 4 ng/ml was found, but a paradoxical inverse relationship was observed in men with a PSA level < 4 ng/ml. Men with a well-differentiated tumour had a 5-year relative survival exceeding 100% regardless of treatment. The survival rate for moderately and poorly differentiated tumours was poor for men managed conservatively. The 10-year cause-specific mortality for patients with PSA 20-50 ng/ml was 36% for patients treated without and 13% for patients treated with curative intent. For patients with a PSA 50-100 ng/ml the 10-year cause-specific mortality was 55% for conservative and 20% for patients treated with curative intent. PCa detection by CNB, magnetic resonance imaging (MR) with ADC (Apparent diffusion coefficient), magnetic resonance spectroscopic imaging (MRSI) and Positron Emission Tomography (PET/CT) ¹¹C Acetate imaging applied to 10 sections of the prostate demonstrated clear conformity between MRI ADC mapping and postoperative findings, showing high specificity (87%) and sensitivity (95%). Conclusion. The inverse relationship between relative survival and PSA at levels below 4 ng/ml should be considered when choosing a PSA cut-off level. Outcome differs little between conservative management and treatment with curative intent in men with localised well- to moderately differentiated tumours over a 10-yr period. For men with poorly differentiated tumours, on the other hand, choice of treatment is crucial for outcome. Treatment with curative intent is beneficial in the group of men with prostate cancer and PSA levels between 20 and 100 ng/ml without distant metastases. A combination of MRI , diffusion ADC and MRSI may provide an improved model for imaging of the prostate for targeted biopsy.
14
Nortcliffe, Andrew. "Nitric oxide donors for the treatment of prostate cancer." Thesis, University of St Andrews, 2013. http://hdl.handle.net/10023/4124.
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Chapter One provides a general introduction into the biology and chemistry of nitric oxide, with particular focus on the role of nitric oxide in cardiovascular disease, cancer and hypoxia. It also details the types of organic functional groups used as nitric oxide donors, with detailed discussion of nitrate esters, furoxans and sydnonimines. Chapter Two discusses prostate cancer. It provides an overview into the development of prostate cancer, prostate cancer staging, and treatment. The key molecular aspects of prostate cancer are detailed, and the types of treatment available outlined. Chapter Three details the synthesis and activity of NCX-1102, a nitric oxide-donating analogue of the non-steroidal anti-inflammatory drug sulindac, and the synthetic work in the preparation of analogues of NCX-1102, using nitrate esters, furoxans and sydnonimines as nitric oxide-donating functional groups. The compounds prepared were tested against a prostate cancer cell line (PC3) and the cytotoxicity results are presented. Chapter Four describes the synthesis of nitric-oxide donating analogues of abiraterone, a CYP17 inhibitor for the treatment of prostate cancer. The results of cytotoxicity assays against PC3 cells are detailed. Chapter Five discusses the application of nitric oxide-donating functional groups in tandem with biologically active motifs. The synthesis of nitric oxide-donating amino acids, and their application to the preparation of nitric oxide-donating RGD peptides and prostate-specific membrane antigen inhibitors is presented, along with representative biological evaluation. Chapter Six introduces possible future work for the continuation of the project, suggesting the synthesis of fluorinated sydnonimines, prostate-specific membrane antigen inhibitors combined with for prostate cancer imaging and a “tool-box” of nitric oxide-donating bioconjugation reagents.
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Hallung, Linda, and Carl-Oscar Scotting. "Upplevelser av biverkningarna vid prostatacancerbehandling." Thesis, Högskolan Väst, Avdelningen för omvårdnad - grundnivå, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:hv:diva-9117.
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Background: Prostate cancer is the most common type of cancer in Sweden. The three primary treatment types for prostate cancer are prostatectomy, radiotherapy and different types of endocrine therapy. With all treatments mentioned above comes adverse effects that may have big effects on the person treated. Aim: The aim of this study was to highlight men´s experiences of the adverse effects that comes with the treatment for prostate cancer. Method: The research method employed was a literature study based on eleven qualitative articles. The method of analysis was done according to Friberg five-step analysis of qualitative articles and through the analysis, six themes emerged. Results: The themes were A feeling of emotional imbalance, Not prepared enough, The experience of loosing control, Feeling of diminished masculinity, The experience of a feminized body and An altered identity. Conclusion: The result showed that men experience adverse effects of the prostate cancer treatment as difficult in many ways. The changes to the body and mental well-being tend to be difficult to deal with, and the men need relevant information prior to treatment to give them time to adjust to their new life.
16
Li, Xing. "Novel brachytherapy techniques for cervical cancer and prostate cancer." Diss., University of Iowa, 2015. https://ir.uiowa.edu/etd/1682.
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Intensity-modulated brachytherapy techniques, compensator-based intensity modulated brachytherapy (CBT) and interstitial rotating shield brachytherapy (I-RSBT), are two novel conceptual radiation therapies for treating cervical and prostate cancer, respectively. Compared to conventional brachytherapy techniques for treating cervical cancer, CBT can potentially improve the dose conformity to the high-risk clinical target volume (CTV) of the cervix in a less invasive approach. I-RSBT can reduce the dose delivered to the prostate organ at risks (OARs) with the same radiation dose delivered to the prostate CTV. In this work, concepts and prototypes for CBT and I-RSBT were introduced and developed. Preliminary dosimetric measurements were performed for CBT and I-RSBT, respectively.
A CBT prototype system was constructed and experimentally validated. A prototype cylindrical compensator with eight octants, each with different thicknesses, was designed. Direct metal laser sintering (DMLS) was used to construct CoCr and Ti compensator prototypes, and a 4-D milling technique was used to construct a Ti compensator prototype. Gafchromic EBT2 films, held by an acrylic quality assurance (QA) phantom, were irradiated to approximately 125 cGy with an electronic brachytherapy (eBT) source for both shielded and unshielded cases. The dose at each point on the films were calculated using a TG-43 calculation model that was modified to account for the presence of a compensator prototype by ray-tracing.
With I-RSBT, a multi-pass dose delivery mechanism with prototypes was developed. Dosimetric measurements for a Gd-153 radioisotope was performed to demonstrate that using multiple partially shielded Gd-153 sources for I-RSBT is feasible. A treatment planning model was developed for applying I-RSBT clinically. A custom-built, stainless steel encapsulated 150 mCi Gd-153 capsule with an outer length of 12.8 mm, outer diameter of 2.10 mm, active length of 9.98 mm, and active diameter of 1.53 mm was used. A partially shielded catheter was constructed with a 500 micron platinum shield and a 500 micron aluminum emission window, both with 180° azimuthal coverage. An acrylic phantom was constructed to measure the dose distributions from the shielded catheter in the transverse plane using Gafchromic EBT3 films. Film calibration curves were generated from 50, 70, and 100 kVp x-ray beams with NIST-traceable air kerma values to account for energy variation.
In conclusion, CBT, which is a non-invasive alternative to supplementary interstitial brachytherapy, is expected to improve dose conformity to bulky cervical tumors relative to conventional intracavitary brachytherapy. However, at the current stage, it would be time-consuming to construct a patient-specific compensator using DMLS, and the quality assurance of the compensator would be difficult. I-RSBT is a promising approach to reducing radiation dose delivered to prostate OARs. The next step in making Gd-153 based I-RSBT feasible in clinic is developing a Gd-153 source that is small enough such that the source, shield, and catheter all fit within a 16 guage needle, which has a 1.65 mm diameter.
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Colbourne, Linda Claire. "Testicular and prostate cancer : explaining the treatment and post treatment experience of couples." Thesis, University of Southampton, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.419165.
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Ockrim, Jeremy Louis. "Transdermal oestradiol therapy for the treatment of advanced prostate cancer." Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.417920.
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DeVita, Lauren M. "An MRI compatible manipulator for prostate cancer detection and treatment." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/39869.
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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2007.Includes bibliographical references (p. 85-91).
Prostate cancer is the most frequently diagnosed cancer in men and the second most common cause of cancer related death in men. Prostate specific antigen (PSA) blood tests and digital rectal exams (DRE) are preliminary tests that can suggest the presence of prostate cancer. Following these tests, a needle biopsy is required to determine if a suspected tumor is benign or malignant. Currently, an ultrasound image is used to help guide a needle to the prostate and to the suspected region. However, ultrasound images are not of good enough quality to accurately hit a tumor. Too often, false negative results are returned because the tumor is missed. This can be prevented by using more accurate images, which can be obtained using Magnetic Resonance Imaging (MRI). This presents a technical challenge because it requires robotic assistance since there is very limited access to a patient inside the bore. Additionally, the high magnetic fields prohibit the use of conventional actuators in the procedure. Dielectric Elastomer Actuators (DEAs) are MRI compatible due to their entirely polymer construction. Studies show that DEAs must be actuated in a bistable manner to be reliable. In this thesis, bistable DEAs were used in the design of an MRI compatible robotic needle manipulator.
(cont.) The concepts of elastic averaging and parallel mechanisms were applied to achieve high precision and adequate stiffness. The manipulator parameters were chosen to fit the specifications established with collaborators at Harvard Medical School's Brigham and Women's Hospital. A design to orient the needle has been developed, analyzed and built. This research shows that the design is feasible for development into a clinical device if manufacturing processes allow for fabrication of multi-layer actuators. Calculations and experiments show repeatability, precision and MRI compatibility.
by Lauren M. DeVita.
S.M.
20
Blanco, Monica Guerrero. "Men's constructions of masculinity following surgical treatment for prostate cancer." Thesis, University of East London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.532602.
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There are a variety of medical approaches to treat prostate cancer. Radical prostatectomy involves the surgical removal of the prostate gland and it has physical consequences. All the participants of this study underwent this medical procedure and were consequently impotent. Erectile problems are a serious matter particularly in a culture where sexuality is the essence of what defines an individual as a man. This study is a qualitative exploration of men's constructions of masculinity after radical prostatectomy. Seven men took part in this study and were recruited through the Urology Department at a National Health Service Hospital. The data was transcribed and analysed using Foucauldian Discourse Analysis. Participants drew on three discourses to refer to their general views of masculinity. They viewed themselves as having been 'mentally resilient' and having an 'indestructible body' which 'functioned naturally'. Once the consequences of treatment were apparent, participants were not able to sustain the view they had of themselves before prostate cancer. They then drew upon discourses of 'vulnerability' to account for the physical changes experienced after treatment. Participants constructed their physical vulnerability drawing on a normalising discourse whereby vulnerability was considered a natural consequence of recovering from an illness and getting older. Lastly, some men were able to separate potency from manliness and felt empowered to reformulate and widen out their construction of masculinity. However their reformulation did not essentially change the hegemonic view of masculinity. It was adapted to bring it closer to what was possible after the operation. The functions, effects and consequences of those constructions are discussed. In addition, the implications of these findings and a critical evaluation of the study are presented.
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Massey, A. "Novel multifunctional delivery systems for the treatment of prostate cancer." Thesis, Queen's University Belfast, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.679224.
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The purpose of this thesis was to evaluate novel protein and peptide based delivery systems for their role in gene therapy and optimisation of anionic drug bioavailability. The recombinant protein D-SMH was found to form small nano-sized particles with plasmid DNA which were capable of specifically targeting prostate cancer cells and achieving transfection efficiencies higher than previous Designer Biomimetic Vectors. Not only was this higher transfection efficiency achieved but neither was it improved in the presence of the endosomolytic agent chloroquine indicating the functionality of the endosomal disruption motif in the sequence. D-SMH presents itself as a candidate for the logical progression past the numerous hurdles in gene delivery including DNA condensation, cell-targeting, cell penetration, endosomal disruption and nuclear localisation. RALA, a 30-mer, arginine-rich peptide was next assessed for its ability to condense siRNA and form nanoparticles capable of transfecting prostate cancer cells. Having confirmed the formation. of small «100nm), positively charged nanoparticles which achieved a transfection efficiency of 95% immediately after a 4 h transfection, the nanoparticles were found to be capable of inducing significant knockdown of the target protein Runx2 in prostate cancer cells with subsequent reduction in cancer cell proliferation. This was translated to the in vivo setting with the pilot study suggesting 80% increase in survival time. Finally, it was hypothesised that since RALA was capable of forming small nanoparticles with anionic nucleic acids, it might also be capable of behaving in the same way with anionic drugs such as the bisphosphonates. The hypothesis was proven as RALA did form small nano-sized particles with the anionic BPs as per a mass ratio. The particles were observed to be stable and induce cell death which was confirmed in vivo with an increase in survival time of 58% compared to control.
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Wall, Bradley A. "Exercise as medicine : reversing treatment toxicities in prostate cancer patients." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2013. https://ro.ecu.edu.au/theses/691.
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A common treatment for prostate cancer, which is the most common form of cancer after skin cancer in Australian males, is androgen deprivation therapy (ADT). However, ADT is associated with an array of adverse effects including reduced bone and lean mass, loss of muscle strength, negative change in lipid profile, and increased risk of cardiovascular disease (CVD) as well as diabetes, all of which can compromise physical function and quality of life. Physical exercise has been suggested as a key lifestyle intervention for this group of cancer patients as it has enormous potential to limit and even reverse the effects of such treatment toxicities. This thesis is comprised of a review of the literature and three experimental chapters examining the effects of androgen deprivation therapy (ADT) and the role of exercise in ADT treated prostate cancer patients. The review of literature provides a background to cancer, in particular prostate cancer and the commonly reported side effects of treatment. The review identified gaps in the literature that highlighted the need for well controlled and longer term experimental studies to: 1) investigate the impact of androgen deprivation therapy duration on cardiovascular and metabolic outcomes, and 2) investigate the effects of a long term exercise intervention in reversing cardiovascular risk factors and unfavourable alterations in the metabolic profile.
Study 1 examined the feasibility and safety of a maximal treadmill exercise test in ADT treated prostate cancer patients as this was a key assessment of physiological response to the exercise intervention. One hundred and twelve prostate cancer patients undergoing ADT took part in a physician supervised multistage maximal stress test (Bruce protocol). Of these men, 85% were able to meet the criteria for the attainment of VO2max whilst three positive tests (3.2%) were observed. The three participants who recorded a positive stress test were sent for further examination and subsequently cleared of any serious issues. Apart from the relatively low VO2max (10-15th percentile), compared to healthy age matched controls, the cardiovascular response to exercise is similar in this cancer population. Maximal exercise testing in this population was demonstrated to be feasible and safe providing a direct assessment of VO2max whilst treatment duration did not appear to influence the cardiovascular responses to exercise.
Study 2 was a cross-sectional design comparing chronic versus acute ADT treated patients to examine if therapy time exposure leads to additional risk factors for CVD and metabolic toxicities in prostate cancer patients. One hundred and seven men undergoing ADT for treatment of prostate cancer were stratified into two groups, either acute (months) or chronic (>3 months) exposure. Chronic ADT exposure was associated with a 17% reduction maximal aerobic capacity (-0.4 L.min-1) and an 8% reduction in resting metabolic rate (-147 kcal/24hr). The chronically exposed group also exhibited 8-22% lower maximal strength values (chest press -5.9kg, seated row -3.9kg, leg press -27.5kg and leg extension -12.2 kg) and a corresponding decrement in physical function variables ranging from 9-16% (400m walk +24.9s, chair rise +2.0s, and stair climb +0.7s). Whilst not significant, there was also a trend towards a decrease in lean mass of 3.5% (-2.1kg) and an increase in fat mass of 6.5% (1.5kg) in the chronically suppressed group. ADT exposure did in fact have a negative effect on CVD risk factors as well as physical function outcomes. Whilst the exact mechanisms remain unclear as to why these cardiovascular alterations and physical function variables are further declining as treatment time progresses, it is possible that factors other than those assessed in this study, such as reduced physical activity levels, may have influenced the results.
Study 3 utilised a randomized controlled trial (RCT) study design to examine the long-term effects (6 months) of a combined aerobic and resistance training intervention in reducing or stabilizing CVD and diabetes risk factors in men receiving ADT. Participants were randomly allocated to either an exercise (EX) group (n= 50) or a control (CON) group (n= 48). The combined aerobic and resistance training program consisted of twice weekly clinic based sessions at which the participants completed 20mins of aerobic activity (70- 90% maximal intensity) and 6 resistance based exercises targeting the major upper and lower body muscle groups. In addition, participants were prescribed a home based training program consisting of 110 minutes of aerobic activity. The control group were instructed to adhere to their usual lifestyle and care routine. Body composition [lean mass 1.1% (+0.8kg), fat mass -4.2% (-1.1kg) & body fat -3.8% (-1.1kg], muscular strength [chest press 9.6% (+3.6kg), seated row 7% (+6.0kg), leg press 14.8% (+20kg) & leg extension 19.4% (+10.2kg)], muscular endurance [chest press 49.4% (+5.0 reps) & leg 49.9% (+7.7 reps)] and 400m walk [-4.8% (-13s)] significantly improved (p
This research has demonstrated that: 1) maximal cardiorespiratory exercise testing is safe and feasible in this population, 2) prolonged exposure to androgen deprivation therapy (>3 months) has a negative impact on a number of cardiovascular, metabolic and physical function outcomes, and 3) a combined aerobic and resistance training program can be safely undertaken in men undergoing ADT and results in an array of benefits for cardiovascular and metabolic outcomes as well physical function. As a result of these findings, patients prescribed ADT for the treatment of prostate cancer should be appropriately counselled as to the negative side effects commonly associated with this form of treatment and be made aware of the safety and beneficial effects an appropriately administered exercise intervention can have on reversing these adverse alterations occurring throughout the course of treatment. Further, these specifically designed exercise interventions should be commenced as soon as practically possible post prostate cancer diagnosis and continue for the course of treatment and ideally beyond.
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Khatami, Ali. "Early prostate cancer : on prognostic markers and predictors of treatment outcome after radical prostatectomy /." Göteborg : Department of Urology, Institute of Clinical Sciences, The Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital, 2007. http://hdl.handle.net/2077/7507.
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Zobalova, Renata. "Novel Treatment of Breast and Prostate Cancer, and Mesothelioma by Targeting Cancer Stem Cells." Thesis, Griffith University, 2013. http://hdl.handle.net/10072/367971.
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Cancer is a major cause of death in the western world and is becoming an increasing world-wide problem. Even though treatment and therapeutic approaches to cancer have become better and there has been great improvement in the diagnosis of this group of pathologies, many cancer types are still lethal as there is no substantial treatment available. Further, even if treatment is successful, there is a significant risk of tumour recurrence, and such a tumour is then even harder to treat due to the acquired resistance in response to exposure to the initial treatment used. Cancer stem cells (CSCs) have been suggested as a reason behind more resistant tumours and tumour recurrence. Hence, CSCs are emerging as an important target for chemotherapy in order to suppress the re-initiation of tumours. The work of this laboratory has focused on two mitocans (mitochondrially-targeted anti-cancer compounds), α-tocopheryl succinate and its
mitochondrially targeted derivative MitoVES. These anti-cancer agents have been shown to be effective against a variety of cancer cells and several in vivo mouse models of cancer, while being non-toxic to normal tissue. Whether they are able to target CSCs was one of the main aims of this study. This thesis addresses several questions in regards to CSCs. Firstly, breast and prostate cancer cell lines (MCF7 and LNCaP, respectively) and a mesothelioma cell line (IstMes2) as well as primary glioblastoma cells grown in the form of spheres were confirmed as a valid model to study CSC biology and resistance to apoptosis, as both phenotypical and genotypical features confirmed increased levels of stemness.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Griffith Health
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Brown, Amy Louise. "Investigation of the relationship between BMI and prostate motion in radiation therapy treatment for prostate cancer." Thesis, Queensland University of Technology, 2015. https://eprints.qut.edu.au/86509/1/Amy_Brown_Thesis.pdf.
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This thesis studied the influence of patient obesity on prostate motion during radiation therapy treatment delivery, an important consideration in the accurate treatment of prostate cancer. The study highlighted the importance of daily image guidance to correct for prostate motion, increasing radiation dose to the prostate while decreasing radiation dose to surrounding healthy tissues, thereby increasing patient quality of life.
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Alibhai, Shabbir Muhammad Husayn. "Do age and comorbidity influence the treatment of localized prostate cancer?" Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ58687.pdf.
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Moussavi, Maryam. "Pre-clinical treatment of prostate cancer using targeted oncolytic viral therapy." Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/33980.
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Prostate cancer is the most prevalent non-skin malignancy and the second leading cause of cancer-related mortality in North American men. Current therapies for patients with locally advanced or metastatic prostate cancer are largely palliative and non-curative. Oncolytic viral-therapy provides a new approach to efficiently target and kill cancer cells while sparing normal cells. Vesicular Stomatitis Virus (VSV) is an oncolytic virus, which can infect and kill cells that have defects in their cellular anti-viral interferon (IFN) response. In this study, enhanced IFN-sensitive VSV(AV3) strain was intra-prostatically injected into two different transgenic mouse models (PTEN-/- and TRAMP) and monitored for infectivity, apoptosis, and innate-immune response. Viral spread and load were monitored by bioluminescence and plaque analysis over 96h time period. It was determined that viral spread begins as early as 3-6h post-viral administration and persisted >72h in prostates of tumour-bearing mice compared to control. Plaque assay provided a similar pattern, with much higher concentrations of replicating virus in prostates and metastatic lymph nodes of tumour-bearing mice compared to control. TUNEL staining of paraffin-embedded prostates and enlarged lymph nodes demonstrated VSV(AV3)’s ability to selectively infect and kill malignant cells while sparing normal cells. This tumour-selective cell death was attributed to a disrupted IFN response in the prostates of tumour-bearing transgenic mice. However, evidence of activated IFN response in the enlarged lymph nodes was observed. To augment the safety of future oncolytic viral-therapies alternate targeting strategy based on tumour-specific over-expression of eIF4E was employed. Three different length of 5’UTRs, which require abundant levels of eIF4E for translation, derived from either fibroblast growth factor-2 (FGF-2) or ornithine decarboxylase were inserted downstream of ubiquitin promoter in a lentiviral-plasmid. Expression of each plasmid was tested in vitro using prostate cancer and control cell lines, and in vivo using PTEN-/- and control mice. Immunofluorescence and Western blot analysis determined FGF-2-5’UTR to be most sensitive to eIF4E levels. Results suggested that control of locally advanced and metastatic prostate cancer may be achievable through intra-prostatic injection and amplification of a safe oncolytic virus, such as VSV(AV3). Also, judicious selection of a complex 5’UTR can enhance viral-based targeted-therapies for prostate cancer.
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Hakenberg, Oliver W., Michael Fröhner, and Manfred P. Wirth. "Treatment of Locally Advanced Prostate Cancer – The Case for Radical Prostatectomy." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133798.
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The treatment of clinically locally advanced prostate carcinoma (stage cT3) remains controversial. One of the main reasons for this controversy results from the substantial staging error attached to the clinical diagnosis cT3 with overstaged T2 tumors and understaged node-positive cases. Treatment options in this situation include radical prostatectomy, external beam radiotherapy, immediate or delayed androgen deprivation treatment and the so-called ‘watchful waiting’. Acceptable and often surprisingly good tumor-specific survival rates have been reported for radical prostatectomy in pT3 series – based on good clinical case selection – approaching those of pT2 series. In lymph node-positive pT3 cases, adjuvant hormone deprivation seems to prolong survival which it does not in lymph node-negative pT3 disease. A benefit of adjuvant external beam radiotherapy after radical prostatectomy for pT3 cases in prolonging overall survival has not been shown, despite the fact that it can prevent or delay biochemical and local recurrence. External beam radiotherapy as the only treatment for cT3 disease results in unfavorable tumor-specific survival rates, which can be significantly improved with adjuvant hormonal treatment with LHRH agonists. If, in case of advanced age and/or significant comorbidity, primary hormonal treatment is chosen, early hormonal deprivation therapy seems to offer marginal benefits in survival compared to delayed treatmentDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Hakenberg, Oliver W., Michael Fröhner, and Manfred P. Wirth. "Treatment of Locally Advanced Prostate Cancer – The Case for Radical Prostatectomy." Karger, 2006. https://tud.qucosa.de/id/qucosa%3A27536.
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The treatment of clinically locally advanced prostate carcinoma (stage cT3) remains controversial. One of the main reasons for this controversy results from the substantial staging error attached to the clinical diagnosis cT3 with overstaged T2 tumors and understaged node-positive cases. Treatment options in this situation include radical prostatectomy, external beam radiotherapy, immediate or delayed androgen deprivation treatment and the so-called ‘watchful waiting’. Acceptable and often surprisingly good tumor-specific survival rates have been reported for radical prostatectomy in pT3 series – based on good clinical case selection – approaching those of pT2 series. In lymph node-positive pT3 cases, adjuvant hormone deprivation seems to prolong survival which it does not in lymph node-negative pT3 disease. A benefit of adjuvant external beam radiotherapy after radical prostatectomy for pT3 cases in prolonging overall survival has not been shown, despite the fact that it can prevent or delay biochemical and local recurrence. External beam radiotherapy as the only treatment for cT3 disease results in unfavorable tumor-specific survival rates, which can be significantly improved with adjuvant hormonal treatment with LHRH agonists. If, in case of advanced age and/or significant comorbidity, primary hormonal treatment is chosen, early hormonal deprivation therapy seems to offer marginal benefits in survival compared to delayed treatment.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Hertzog, Jennifer R. "Molecular Characterization of AR Antagonist Resistance During Treatment of Prostate Cancer." Thesis, University of the Sciences in Philadelphia, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=28156175.
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Prostate cancer is the most commonly diagnosed cancer in men and nearly 30,000 patients will die this year due to complications arising from the disease. Prostate cancer patients are frequently treated with androgen deprivation therapies, but the duration of response is variable, and patients frequently progress to an incurable stage of the disease referred to as castration-resistant prostate cancer (CRPC). Second-generation AR antagonists such as enzalutamide and apalutamide are effective therapies that block androgen receptor (AR) transactivation and signaling in over 50% of CRPC patients. However, an estimated 30% of responders will develop resistance to these therapies within two years. There is another class of AR antagonists which are referred to as pan AR antagonists, that have shown to inhibit the activity of wild-type AR as well as several mutated versions of AR. Currently, there are several pan AR antagonists in preclinical development and approved for the treatment of CRPC in patients harboring pathogenic point mutations in AR. We chose four genetically distinct AR-positive prostate cancer preclinical models to generate enzalutamide, JNJ-pan-AR, or apalutamide resistant cell lines. We then performed transcriptomic and proteomic profiling on the AR antagonist sensitive and resistant cell lines to uncover molecular alterations that may be critical to the maintenance and/ or predictive biomarkers of the resistant phenotype. Global profiling uncovered significant variability in molecular alterations across the AR antagonist resistant cell lines as well as the prostate cancer preclinical models. However, we uncovered upregulation of AKR1C3 protein expression across all three AR antagonist resistant cell lines using the LNCaP and LNCaP/AR preclinical models. Further characterization of the functional significance of AKR1C3 upregulation demonstrated that AKR1C3 protein expression contributes to JNJ-pan-AR resistance. Similar findings have reported the correlation between AKR1C3 expression and changes in drug efficacy across several chemotherapeutic agents approved to CRPC treatment. Collectively the findings from this study support the rationale of AKR1C3 as a target for AR antagonist resistant prostate cancer disease progression.
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Murray, Louise Janet. "Optimising treatment outcomes using Stereotactic Body Radiotherapy (SBRT) for prostate cancer." Thesis, University of Leeds, 2014. http://etheses.whiterose.ac.uk/8666/.
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Aims: to optimise linear accelerator-based prostate stereotactic ablative radiotherapy (SABR) through planning studies, tumour control probability (TCP) and normal tissue complication probability (NTCP) calculations and radiation-induced second primary cancer (RISPC) risk assessment. Methods: A planning study was performed to develop a class solution for prostate SABR. A second planning study delivered boosts to dominant intra-prostatic lesions (DILs) and TCP and NTCP were calculated. A third planning study compared prostate SABR planning using flattened and flattening filter free (FFF) beams. A systematic review examined RISPC risk following prostate radiotherapy. A final study estimated RISPC risks following prostate SABR in comparison to other contemporary radiation techniques. Results: Prostate SABR was optimal using a single anterior arc which resulted in highly conformal plans, lower rectal doses and improved delivery times and monitor unit requirements for most patients. Boosting DILs resulted in small TCP increases, but the benefit was offset by increases in NTCP. SABR to the whole prostate without DIL boosting resulted in high TCP and low NTCP. Plans using flattened and FFF beams were dosimetrically similar but FFF resulted in reduced delivery times. Clinical evidence, largely based on older radiation techniques, suggests that prostate radiotherapy increases RISPC risk. Clinical evidence concerning risk following modern techniques is too immature to draw firm conclusions. The final study demonstrated that SABR techniques resulted in lower estimated RISPC risks in all organs compared to conventionally fractionated techniques, while FFF techniques reduced RISPC risks in out-of-field organs. Conclusions: Linear accelerator-based prostate SABR delivered with a single partial arc is optimal and high levels of TCP and low levels of NTCP are predicted from whole prostate SABR. FFF allows faster treatment delivery. Second malignancy risk is lower using SABR, particularly with FFF, compared to conventionally fractionated techniques. Phase III trials are required to investigate prostate SABR in practice.
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McGoldrick, Christopher Allen. "Novel Ester Substrates for the Detection and Treatment of Prostate Cancer." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etd/2308.
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Cancer cell esterases are often overexpressed and some have chiral specificities different from those of corresponding normal cells. Carboxylesterases in particular are known to be overexpressed in several cancers. Additionally, cancer cells often exhibit high levels of intrinsic oxidative stress that is required for survival and an aggressive phenotype. We hypothesized that these 2 characteristics of cancer cells could be exploited to aid in the detection and treatment of prostate cancer. We have developed a fluorogenic ester probe that is activated by carboxylesterase to help distinguish tumorigenic cells from nontumorigenic prostate cells. Ester prodrugs have the same activation mechanism and have been thought to be a promising approach in cancer therapy. Prodrugs are inactive drugs that can be selectively activated by a specific enzyme. We have developed a chiral ester prodrug strategy using native polyacrylamide gel electrophoresis (n-PAGE) and proteomic methods to compare and identify the esterase profiles of several tumorigenic and nontumorigenic prostate cell lines. Our results showed that cell lysates from LNCaP, DU 145, and PC3 prostate cancer cell lines exhibit differential esterase activity compared with non-tumorigenic RWPE-1 prostate cell lysates when incubated with α- naphthyl acetate or α-naphthyl N-acetyl-alaninate ester substrates and a diazonium salt. We have identified oxidized protein hydrolase (OPH), a serine esterase/protease that catalyzes the removal of N-acylated residues from proteins, to be differentially expressed between some tumorigenic and nontumorigenic prostate cell lines. OPH was found to have high hydrolytic activity towards the S-isomer of α-naphthyl N-acetylalaninate (S-ANAA) chiral ester. LNCaP lysates incubated with N-acetyl-alanyl-p-nitroanilide, a known OPH substrate, had twofold higher OPH activity compared with RWPE-1 lysates. We have also developed and tested novel glutathione depleting prodrugs modeled after S-ANAA that increase oxidative stress and induced apoptosis in tumorigenic prostate cells with little effect on nontumorigenic RWPE-1 cells. These results suggest that ester molecular beacon probes and ester prodrugs may be effective in identifying and treating prostate cancer tumors that overexpress esterases with little effect on normal prostate cells.
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Schumacher, Oliver. "Exercise as adjunct therapy during treatment for men with prostate cancer." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2022. https://ro.ecu.edu.au/theses/2540.
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Background: Radiation and hormone therapy, either alone or in combination, are standard treatments for prostate cancer that improve patient outcomes. However, they are associated with significant adverse effects that can impact quality of life. Moreover, a substantial number of patients will experience disease recurrence that may require further treatment, resulting in additional side effects. Exercise medicine has been identified as a potential strategy to mitigate treatment-related toxicities. In addition, results from preclinical studies indicate that exercise can modulate the tumour microenvironment and thereby improve radiotherapy treatment efficacy. However, most exercise studies for men with prostate cancer have either been conducted in patients on hormone therapy or in relation to surgery and there is a dearth of knowledge regarding the potential benefit of exercise during radiotherapy. Furthermore, there are no published studies that have investigated and confirmed the acute tumour modulatory effect of exercise in a clinical population.
Purpose: The purpose of this doctoral research was to explore the utility of exercise as an adjunct therapy for prostate cancer patients undergoing treatment, with a particular focus on radiotherapy and the implementation of exercise programs into standard clinical care pathways.
Methods: This thesis comprises three interrelated parts. Part 1 is a systematic review with meta-analysis and a secondary data analysis of two randomised controlled trials where the effects of exercise on physical function as well as treatment-related side effects in men with prostate cancer during radiotherapy were investigated. In Part 2, I discuss the potential role of exercise to improve the response to radiotherapy in prostate cancer patients through modulation of tumour perfusion and oxygenation. Furthermore, I investigate the effect of an acute bout of 10-15 minutes of moderate-to-vigorous-intensity step exercise on tumour perfusion using magnetic resonance imaging. Finally, in Part 3, I assess the feasibility of aerobic and lower-body resistance exercise training immediately before radiotherapy fractions in men with prostate cancer undergoing 4-8 weeks of external beam radiation therapy and expand on the notion of treatment-integrated delivery of exercise programs. The latter comprises an analysis of a nationwide industry-led community-based patient support initiative for men with locally advanced, relapsed or metastatic prostate cancer receiving Lucrin® – The Man Plan® Program.
Results: In Part 1, we found exercise to be an effective intervention to mitigate urinary toxicity and fatigue during radiotherapy for prostate cancer. Furthermore, multimodal exercise resulted in significant improvements in cardiorespiratory fitness and upper and lower-body muscle strength. In Part 2, there was preliminary evidence for exercise to acutely increase tumour perfusion in men with prostate cancer. Moreover, the results in Part 3 support the feasibility of treatment-integrated, pre-radiotherapy exercise training for prostate cancer patients. Additionally, the investigation revealed that The Man Plan® Program is an effective intervention to prevent weight gain, reduce blood pressure and improve physical function.
Conclusions: Exercise is an effective strategy to improve physical function and manage treatment-related toxicity in prostate cancer patients undergoing radiation and hormone therapy. Furthermore, the findings from this thesis provide new insights into the potential impact of exercise on the tumour microenvironment.
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Sutherland, Sarah. "A novel dendritic cell vaccine for the treatment of prostate cancer." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/28701.
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Prostate cancer (PCa) is the most common cancer diagnosed in Australian males and the second most common cause of death (1). The mainstay of PCa treatment has been hormonal therapy, initially with androgen ablation by either chemical or surgical castration. In recent years, novel anti-androgens have led to improved overall survival (OS) (2-6) as has bringing these agents and docetaxel earlier in the time course of metastatic disease to before androgen resistance has occurred (7-9). However, ultimately treatment resistance still occurs, and new therapies are required for this common disease.
Immunotherapy to date has had disappointing results in PCa with trials of CTLA-4 and PD-1 inhibitors failing to improve OS (10-12). In contrast Sipuleucel-T, a dendritic cell (DC) based vaccine, did improve OS (13). However, its uptake in practice has been limited, in part due to the cost and expertise required to deliver an autologous cellular based vaccine. In this body of work I first review progress in DC vaccine technology with particular focus on PCa. From this I propose that targeting DC with tumour antigen in situ is a promising strategy to optimise DC vaccine deliverability and enhance efficacy.
I assess two methods of targeting DC in situ. Nanoparticles using polyhydroxybutyrate (PHB) beads gifted by our collaborators, Bernd Rehm at Griffith University (14) and antibody directed antigen uptake. The nanoparticles were quickly taken up by DC but did not induce an antigen specific immune response. I then identify a panel of antibodies that target DC for their ability to internalise, expression on DC and monocytes, lack of expression on human tissue and ability to produce an antigen specific immune response. From this panel I put forward Dendritic Cell Research mAb number 2 (DCR-2), a monoclonal antibody against human (h)CD300f as the best to target DC. This mouse antibody was then humanized and manipulated to express the prostate antigen PSMA in its fragment crystallizable (Fc) region. This antibody retained its ability to bind CD300f and internalise. In one experiment I show that hDCR-2 with PSMA produces an anti-PSMA T cell response.
CD300f is an immune modulatory molecule that is part of the CD300 family. We know that DCR-2 leads to conformational change in CD300f and thus I hypothesised that DCR-2 may affect the phenotype and function of DC and monocytes. I show that DCR-2 leads to activation of DC, increases their ability to migrate and increases their ability to stimulate T cells in an MLR. In contrast, on monocytes DCR-2 increased PD-L1 expression and suppressed T cell proliferation in a monocyte suppressor assay.
Lastly, I look at our DC vaccine in the context of PCa. Are the DC present in PCa, are they affected by treatment, and do they express our target CD300f? Monocyte and T cell phenotype and function can influence the efficacy of a DC vaccine. I determine the presence and phenotype of monocytes and T cells in PCa, I assess the impact of treatment with docetaxel chemotherapy and the novel therapy ribociclib on immune cells. Lastly, I look at the effect of patient serum on monocyte and DC function and determine whether macrophage inhibitory cytokine 1 (MIC-1) is contributing to immune evasion in PCa.
In this thesis I have made a novel DC vaccine for PCa. I show that this can produce an antigen specific immune response in vitro. I show that this DC vaccine skews DC towards a more active phenotype with improved chemotaxis and increased ability to stimulate T cells. I show that that those simulated T cells demonstrate increased IFNγ production suggesting, a Th1 response. I explore when to use this vaccine in PCa and show that there are more DC present in localized PCa (LPCa) with less myeloid derived suppressor cells (MDSC) suggesting a DC vaccine early in the course of PCa maybe more effective.
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Adeola, Henry Ademola. "Novel urinary and serological markers of prostate cancer using proteomics techniques: an important tool for early cancer diagnosis and treatment monitoring." Doctoral thesis, University of Cape Town, 2016. http://hdl.handle.net/11427/20955.
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In Africa, Prostate cancer (PCa) is the most frequently diagnosed solid organ tumour in males and use of prostate specific antigen (PSA) is presently fraught with diagnostic inaccuracies. Not least, in a multi-ethnic society like South Africa, proteome differences between African, Caucasian and Mixed-Ancestry PCa patients are largely unknown. Hence, discovery and validation of affordable, non-invasive and reliable diagnostic biomarkers of PCa would expand the frontiers of PCa management. We have employed two high-throughput proteomics technologies to identify novel urine- and blood-based biomarkers for early diagnosis and treatment monitoring of prostate cancer in a South African cohort as well as elucidate proteome differences in patients from our heterogeneous cohort. We compared the urinary proteomes of PCa, Benign Prostatic Hyperplasia (BPH), disease controls comprising patients with other uropathies (DC) and normal healthy controls (NC) both by pooling and individual discovery shotgun proteomic assessment on a nano-Liquid chromatography (nLC) coupled Hybrid Quadrupole-Orbitrap Mass Spectrometer platform. In-silico verification of identified biomarkers was performed using the Human Protein Atlas (HPA) as well as SRMAtlas; and verified potential biomarkers were experimentally prevalidated using a targeted parallel reaction monitoring (PRM) proteomics approach. Further, we employed the CT100+ antigen microarray platform to assess the differential humoral antibody response of PCa, DC and BPH patients in our cohort to a panel of 123 tumour-associated cancer antigens. Candidate antigen biomarkers were analyzed for ethnic group variation in our cohort and potential cancer diagnostic and immunotherapeutic inferences were drawn. Using these approaches, we identified 5595 and 9991 non-redundant peptides from the pooled and individual experiments respectively. While nine proteins demonstrated ethnic trend, 37 and 73 proteins were differentially expressed by pooled and individual analysis respectively. All 32 verified biomarkers were prevalidated with parallel reaction monitoring. Good PRM signals for 12 top ranking biomarker was observed, including PSA and prostatic acid phosphatase. We also identified 41 potential diagnostic and immunotherapeutic antigen biomarkers. Proteogenomic functional pathway analyses of differentially expressed antigens showed similar enrichments of biologic processes. We identified herein novel urinary and blood-based potential diagnostic biomarkers and immunotherapeutic targets of PCa in a South African PCa Cohort using multiple proteomics approaches.
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Ávila, Pacheco Mónica Marcela 1984. "Comparative effectiveness research on localized prostate cancer treatmens." Doctoral thesis, Universitat Pompeu Fabra, 2017. http://hdl.handle.net/10803/587145.
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This thesis performs the comparison on patient-reported outcomes (health-related quality of life and patients’ preferences) among radical prostatectomy, external radiotherapy and brachytherapy, in the “Spanish Multicentric Study of Clinically Localized Prostate Cancer”. This is a prospective cohort with consecutive patient recruitment at diagnosis (2003-2005) in 10 hospitals. The impact of the treatments on HRQoL at 5-year follow-up was characterized obtaining directly from the cohort patients their health-related quality of life measured with the Expanded Prostate Index Composite (EPIC), one of the most established instruments among prostate cancer-specific ones. Also patients’ preferences obtained by direct methods, including time trade off, standard gamble and willingness to pay were described. Finally, psychometric properties of the Spanish version of the Patient-Oriented Prostate Utility Scale (PORPUS), the first econometric instrument developed for measuring utilities by the indirect method on patients with localized prostate cancer, were evaluated.Esta tesis hace la comparación de los resultados percibidos por los pacientes, calidad de vida relacionada con la salud (CVRS) y preferencias, entre la prostatectomía radical, radioterapia externa y braquiterapia, en el "Estudio Multicéntrico Español de Cáncer de Próstata Localizado”, una cohorte prospectiva de pacientes reclutados en 10 centros hospitalarios (2003-2005). El impacto de los tratamientos sobre la CVRS de los pacientes fue caracterizado y medido a los 5 años de seguimiento con el “Expanded Prostate Index Composite” (EPIC), uno de los instrumentos específicos para cáncer de próstata más utilizados. Las preferencias de los pacientes también fueron estimadas, a través de métodos directos como el “time trade-off”, “standard gamble” y “willingness to pay”. Finalmente, se evaluaron las propiedades psicométricas de la versión española del “Patient-Oriented Prostate Utility Scale” (PORPUS), el cual es el primer instrumento econométrico desarrollado para la estimación indirecta de utilidades en pacientes con cáncer de próstata localizado.
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Ouvinha, De Oliveira Rachel. "Development and evaluation of nanoparticles for cancer treatment." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA114808/document.
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Cette thèse concerne le développement et l'évaluation des nanoparticules pour le traitement du cancer et plus particulièrement pour le cancer de la prostate.Le manuscrit comprend une revue de la littérature sur l'application de la nano médecine pour le traitement du cancer de la prostate. Dans la première partie expérimentale, des nanoparticules d'or fonctionnalisées ont été caractérisées et chargées avec le docétaxel par adsorption non covalente.Ces nanoparticules d'or ont montré un effet cytotoxique in vitro prolongé contre les cellules cancéreuses de la prostate. La deuxième partie expérimentale de cette thèse décrit une étude de synthèse et une nano-précipitation de polyesters pour la co-délivrance de deux médicaments chimio-thérapeutiques, le docétaxel (DOC) et la mitoxantrone (MIT). Les polycaprolactone, poly(acide lactique) et poly(lactide-co-glycolide) ont été synthétisés par polymérisation par ouverture de cycle avec des poids moléculaires différents de polyéthylène glycol. Des nanoparticules monodisperses d’un diamètre d’environ 80 nm ont été obtenues et se sont avérées être efficaces contre les cellules cancéreuses de la prostate quand cela est chargé en MIT et DOC. De plus, un effet synergique a été observé en utilisant des combinaisons de ces nanoparticules. Par conséquent, ces nanoparticules, à base de polyester, ont de potentielles applications cliniquesThis thesis concerns the development and evaluation of nanoparticles for cancer treatment, and in particular to prostate cancer. The manuscript includes a literature review on the application of nanomedicine to the treatment of prostate cancer. In the first experimental part, functionalized gold nanoparticles were characterized and loaded with docetaxel by non covalent adsorption. These gold nanoparticles showed a sustained cytotoxic effect in vitro against prostate cancer cells. The second experimental part of this thesis describes a study of synthesis and nanoprecipitation of polyesters for the co-delivery of two chemotherapeutic drugs, docetaxel (DOC) and mitoxantrone (MIT). Polycaprolactone, poly(lactic acid) and poly (lactide-co-glycolide) were synthesized by ring-opening polymerization with different molecular weights of polyethylene glycol. Monodisperse nanoparticles with diameters of less than 80 nm were produced and were shown to be effective against prostate cancer cells when loaded with MIT and DOC. Moreover, a synergistic effect was observed using combinations of these nanoparticles. Therefore, these polyester based nanoparticles have potential clinical applications
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Chen, Weihua. "Role of RhoA/ROCK pathway in angiogenesis and their potential values in prostate cancer treatment." Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05T047/document.
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Le cancer de la prostate est la principale cause de décès chez les hommes des pays occidentaux. Traitement du cancer de la prostate résistant à la castration (CRPC) métastatique est encore limité. RhoA/ROCK sont les régulateurs principaux du cytosquelette et sont impliqués dans l'angiogenèse et l'invasion tumorale. Dans la première étude (partie 1), nous avons étudié les effets anti-angiogéniques de fasudil ( inhibiteur de ROCK ) in vitro. Des cellules endothéliales de la veine ombilicale sont stimulé par les cellules du cancer de la prostate. La prolifération est détectée par la Bromodéoxyuridine (BrdU). La migration est détectée par la cicatrisation des plaies. Les conditions de l'angiogenèse in vitro sont évaluées par la formation des tubes et un ellipsoïde test de germination. Fasudil inhibe la prolifération et la migration des cellules endothéliales induite par le cancer de la prostate. Dans les tests in vitro de l'angiogenèse, les formations des tubes et des germes sphériques sont inhibées significativement par fasudil dans d'une manière dépendante de la dose. Selon les résultats de Western Blot, l'expression de MYPT-1 a été significativement réduite après le traitement de Fasudil, confirmé l'inhibition de l'activité de ROCK par fasudil. Dans la deuxière étude (partie 2 et 3), l'expression et l'activité de RhoA sont évaluées chez 34 tissues paraffinées et 20 échantillons congelés de la prostate, obteni de 45 malades du cancer de la prostate qui à été reçu une prostatectomie radicale. Les motifs de l'expression de RhoA sont detecté par la coloration immunomarquage et western blot. Les différence entre le centre, l'avant et plus loin autour de la tumeur sont évalué. L’activité de RhoA sont évalué par G-LISA. Le gradient d'augmentation de l'expression de RhoA a été trouvé du centre a la region autour de la tumeur. L'expression de RhoA est supérieure significativement dans les cellules de l’avant de la tumeur par rapport au centre de la tumeur par Immunohistochimie (p = 0001). Gleason score était significativement supérieur chez des patients avec l'expression de RhoA élevée dans l’avant et centre de la tumeur (p =0044 et 0039, respectivement). Après un suivi médian de 52 mois, le taux de récidive est plus élevé chez des patients avec l'expression de RhoA élevée dans l’avant de la tumeur (62,5% contre 35%), une tendance évidente a la différence significative (P = 0089). Il n'y a pas de corrélation entre l'expression de RhoA, PSA et la stadification pathologique. On a aussi découvert que l'expression de le ROCK2, mais pas l'expression de le ROCK1, est eleve significativement dans l’avant de la tumeur du cancer de la prostate. En conclusion, nous avons trouvé que fasudil inhiber la prolifération, la migration, la formation de capillaires et de la sphère de la germination des cellules endothéliales vasculaires d’'une manière dépendante de la dose. Ces effets peut-être grâce à l'inhibition de l'activité de la ROCK résultant de la sécrétion de cellules du cancer de la prostate. Nous avons aussi trouvé que l'expression de la RhoA et ROCK2 dans l’avant de la tumeur de la prostate sont plus élevés. La corrélation de l'expression de RhoA avec Gleason score et récidive est identifiée. Cela montre l’association entre la voie RhoA/ROCK et l’agressive du cancer de la prostate. L'étude décrite ici peut fournir de nouveaux traitements cible la voie RhoA/ROCK contre l’angiogenèse et agressive du cancer de la prostate. Fasudil peut être utile comme agent anti - angiogénique, doit être étudiée pour leur rôle potentiel dans le traitement du cancer de la prostateProstate cancer remains a major cause of mortality among males in western countries. Treatment options for metastatic castration-resistant disease remain limited. There is a continuing unmet need for new systemic interventions in patients with progressive prostate cancer. RhoA/Rho-associated protein kinases (ROCK) are key regulators of the cytoskeleton and have been implicated in PCa angiogenesis and tumour invasion. In the first study (Part I), we investigated the anti-angiogenic effects of fasudil, a ROCK inhibitor, on PCa-induced angiogenesis in vitro. Proliferation of PCa-conditioned human umbilical vein endothelial cells (HUVECs) was assessed using a bromodeoxyuridine (BrdU) assay, and migration was assessed with a wound healing assay. In vitro angiogenesis of PCa-conditioned HUVECs was evaluated by tube formation and a spheroid sprouting assay. Fasudil inhibited PCa-induced endothelial cell proliferation, and also decreased PCa-induced endothelial cell migration. In the in vitro angiogenesis assay, tube formation and spheroid sprouts were significantly inhibited at fasudil in a dose dependent manner. Western blotting results showed that expression of phosphorylated myosin phosphatase target subunit 1 (MYPT-1) was significantly lower after fasudil treatment, confirming that fasudil inhibited ROCK activity in these model systems. In the second study (Part II & III), we evaluated RhoA expression and activity in a total of 34 paraffin embedded and 20 frozen prostate specimens, respectively, obtained from 45 patients treated with radical prostatectomy for clinically localized cancer. The expression patterns of RhoA were tested by immunohistochemical staining and Western blotting, and further compared between the tumour centre, tumour front and distant peritumoral tissue. RhoA activity was assessed by G-LISA. Our results showed an increasing gradient of expression from the centre to the periphery of index tumour foci. RhoA expression was indeed significantly higher at the tumour front as compared to tumour centre, using immunohistochemistry (p=0.001). Gleason score was significantly higher in the patients with higher RhoA expression in both the tumour front and tumour centre (p=0.044 and 0.039, respectively). After a median follow-up of 52 months, the rate of PSA relapse was higher in patients with a higher RhoA expression at the tumour front (62.5% vs 35%), although the difference was not significant (p=0.089). There was no association between RhoA expression and PSA, pathological stage. We also found ROCK2 expression, but not ROCK1 expression, was significantly higher in the prostate cancer tumor front. In conclusion, we found fasudil significantly inhibits the key steps of endothelial cell angiogenesis, including proliferation, migration, capillary tube formation and spheroid sprouting, in a dose-dependent manner. These effects may due to inhibition of ROCK activity induced by PCa cell secretions. We also identified higher RhoA and ROCK2 expression in human prostate tumour front. The correlation of higher RhoA expression with higher Gleason score and higher rate of cancer relapse. This indicated the association of RhoA/ROCK2 pathway with aggressiveness of prostate cancer. The insights described here may provide the foundation for novel therapeutic approaches targeting RhoA/ROCK pathway to inhibit angiogenesis and clinically aggressiveness of PCa. Fasudil may be a useful anti-angiogenic agent and should be investigated further for its potential role in PCa treatment
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Frisk, Jessica. "Acupuncture treatment for hot flushes in women with breast cancer and men with prostate cancer." Doctoral thesis, Linköpings universitet, Obstetrik och gynekologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-68806.
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Background: The group of women and men with a history of cancer and distressing hot flushes and sweating is growing. The flushes negatively affect Health Related Quality of Life (HRQoL), perhaps partially by disturbing sleep. Treatments that are effective, tolerable and safe need to be developed. There are a number of treatment alternatives that are often not very effective or associated with more or less serious side-effects. Based on theories on the mechanisms behind hot flushes and acupuncture, treatment with acupuncture has been tried in menopausal women with hot flushes and in a few studies in women with breast cancer (BCa). Aim: The general aim of the research leading to this thesis was to evaluate the effect of acupuncture on hot flushes, HRQoL and sleep in men with prostate cancer (PCa) and women with BCa. To evaluate the effect in women with BCa of 12 weeks of electrostimulated acupuncture (EA) and two years of hormone therapy (HT) on number of, and distress caused by, hot flushes, and on HRQoL and sleep. To evaluate whether acupuncture therapy could be used to treat hot flushes in men with PCa treated with castration therapy, and then to evaluate in men with PCa and hot flushes the effect of 12 weeks of traditional acupuncture (TA) or EA on number of, and distress caused by, hot flushes and on urinary excretion of CGRP, HRQoL and sleep. Subjects and methods: Forty-five women with a history of BCa were randomized to oral HT for two years or EA for 12 weeks and were followed up till two years after start of therapy. Thirty-eight men with PCa and hot flushes were treated with acupuncture. Seven men were treated with EA for 10 to 12 weeks in a pilot study. After positive results from this study 31 men were randomized between EA and TA for 12 weeks and followed up till nine months after end of treatment. Hot flushes, HRQoL and sleep were monitored by means of log books and validated questionnaires. Results: The pilot study showed that 10 to 12 weeks of EA in men with PCa reduced number of hot flushes to below 50% of baseline with persistent effects at a follow up three months later. The two randomized studies showed that treatment with acupuncture in women with a history of BCa, and men with PCa was associated with a decrease in both the number of and distress caused by hot flushes by at least 50%. HT almost eliminated the hot flushes. There was no difference in reduction of hot flushes between men receiving EA or TA. Reduction of the number of hot flushes and distress caused by hot flushes probably leads to decreased disturbances at night, and was associated in women with a significant improvement in HRQoL and sleep variables. The improvement in HRQoL was as great in women treated with EA as in women receiving HT although the latter group had a more substantial reduction in number of flushes than the EA group suggesting that EA might have other effects in addition to those on hot flushes. In the men HRQoL did not change significantly. We saw very few and non-serious side-effects in the acupuncture groups and no signs that acupuncture activated the cancer or ovarian/testicular function. Conclusions: Acupuncture reduced the number of hot flushes and distress caused by hot flushes with at least 50% in women and men with hot flushes and a cancer disease and also improved HRQoL and sleep at least in women. Acupuncture should be further evaluated in these patient groups and could be a treatment alternative in patients with troublesome symptoms.
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De, Armas Ricardo Eduardo. "Impact of intrafractional prostate motion on the accuracy and efficiency of prostate cancer treatment on CyberKnife radiotherapy." Thesis, Massachusetts Institute of Technology, 2015. http://hdl.handle.net/1721.1/98920.
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Thesis: S.B., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2015.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 39-41).
One of the most common treatments for men with localized prostate cancer is radiation therapy, which involves delivering small doses of radiation to the prostate for an extended period of time. Stereotactic-body radiation therapy (SBRT) is a form of radiotherapy that delivers increased dosage to the prostate with more precision. The results are shorter treatment times, increased effectiveness, and less toxicity to surrounding tissue. However, the prostate has been found to move around during treatment (intrafraction) and between treatments (interfraction). With greater precision, there is a greater risk of missing the target while the prostate is moving. This study assesses the impact of intrafractional prostate motion on the accuracy and efficiency of SBRT on CyberKnife. Prostate tracking log files were acquired from 6 patients with prostate cancer, which comprises18 SBRT fractions and 1,892 X-ray image registrations. Each image contains real-time prostate motion in 6D. The data were compared against clinically used margins to identify periods of large prostate motion during treatment. Results indicate significant periods of prostate motion, with the greatest movement occurring in anterior-posterior translation (6.2% outside margin) and pitch rotation (4.3% outside margin). The percentage of prostate motion beyond margins varied among patients, with an average of 12.8% outside clinical margins and 36.0% outside hypothetically reduced margins. The treatment time for each fraction was also recorded to quantify the efficiency of CyberKnife delivery. Because of motion-related delays, optimal setup of 5-15 minutes was seen in only 50% of the fractions, and optimal beam delivery times of 30-40 minutes in 44% of fractions. Thus, results suggest that treatment accuracy and efficiency were negatively affected by the occurrence of large prostate motion. Techniques that immobilize the prostate during treatment may be considered to reduce intrafractional prostate motion and ensure greater accuracy and efficiency of prostate cancer SBRT.
by Ricardo Eduardo De Armas.
S.B.
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Holmström, Benny. "Early diagnosis and treatment of prostate cancer : observational studies in the National Prostate Cancer Register of Sweden and the Västerbotten Intervention Project." Doctoral thesis, Umeå universitet, Urologi och andrologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-42843.
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Prostate-specific antigen (PSA) testing has caused a steep increase in the incidence of prostate cancer, especially the incidence of localised low risk disease. In order to decrease the overdiagnosis accompanied by PSA testing, analysis of inherited genetic variants have been suggested as potential tools for clinical assessment of disease risk. With the aim of minimizing overtreatment and postpone side-effects of curative treatment for low risk prostate cancer, active surveillance, a treatment strategy with initial surveillance and deferred radical prostatectomy at the time of progression has evolved. The aim of this thesis was to study the validity of PSA (paper I) and inherited genetic variants (paper II) for early diagnosis of prostate cancer, to assess the extent of PSA testing in Sweden (paper III), and to study the safety of deferred radical prostatectomy in localised low to intermediate risk prostate cancer (paper IV). The study designs were i) case-control studies nested within the Västerbotten intervention project (paper I and II), ii) observational study in the Cancer Register of Sweden (paper III), and iii) observational study in the NPCR Follow-up study (paper IV). PSA had a high validity in predicting a prostate cancer diagnosis with an area under the receiver operating characteristics (ROC) curve of 0.86 (95% CI, 0.84 to 0.88). A combined test, including PSA, the ratio of free to total PSA, and 33 single nucleotide polymorphisms (SNPs) in a genetic risk score, increased the area under curve to 0.87 (95% CI, 0.85 to 0.89). The estimated uptake of PSA testing among men aged 55 to 69 years increased from zero to 56% between 1997 and 2007 and there were large variations in the uptake of PSA testing between counties in Sweden. After a median follow-up time of eight years there was no significant difference in presence of any one or more adverse pathology features or prostate cancer specific mortality after primary compared to deferred radical prostatectomy in localised low to intermediate risk prostate cancer. Results from these studies indicate that PSA and the hitherto identified SNPs are not suitable biomarkers in single-test prostate cancer screening. It is possible to estimate the uptake of PSA testing on a population level. Initial surveillance and deferred radical prostatectomy represent a feasible treatment strategy in localised low to intermediate risk prostate cancer.
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Stewart, Grant Duncan. "Novel survival factors and approaches to the treatment of hypoxic prostate cancer." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/4390.
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Tumour hypoxia has been demonstrated to cause development of an aggressive tumour phenotype and is associated with increased patient mortality and poorer response to treatments such as chemotherapy and radiotherapy. Previous studies have established that hypoxia exists within a nidus of prostate cancer. Based on the importance of the tumour microenvironment, especially hypoxia, in prostate cancer, the major aims of this thesis were to establish: (a) the role of a novel putative survival factor, dermcidin, in prostate cancer survival under hypoxia/oxidative stress; and (b) the effect of nitric oxide-donating non-steroidal anti-inflammatory drugs (NO-NSAIDS), a new class of drugs, on the killing of prostate cancer cells subjected to hypoxia. A wide-range of confirmatory, cellular and molecular biology techniques were employed in this thesis. The PC-3 hormone-insensitive prostate cancer cell line was used for the majority of studies as this cell line represents hormone-independent prostate cancer, treatment of which is currently palliative. Cell incubation at 0.2% oxygen for 48 hours was established as suitable conditions to stimulate the development of the hypoxia response. Upregulation of nuclear hypoxia-inducible factor-1α protein was the main marker used to assess the hypoxia response. Dermcidin messenger RNA production was found to occur in a range of prostate cancer cell lines; was upregulated in cell lines by both hypoxic and oxidative stress; and found to act as a proliferation, survival and pro-invasion factor under hypoxia and oxidative stress in immortalised prostate cancer cell lines. Furthermore, the portion of the dermcidin molecule responsible for the survival advantage was localised to the proteolysis-inducing factor core peptide subunit. However, subsequent analysis of primary cancer samples from prostate cancer patients revealed that dermcidin was not expressed in these tumours, although dermcidin mRNA was identified in analysis of other primary tumours. As such, the role of dermcidin in prostate cancer was not evaluated further in this thesis. Investigation of NO-sulindac (a NO-NSAID drug) in hypoxic PC-3 cells showed that these agents were significantly more pro-necrotic, pro-apoptotic and anti-invasive than traditional, unnitrated sulindac. NO-sulindac was found to downregulate the hypoxia response mounted by PC-3 cells under hypoxia via the Akt signalling pathway. Finally, analysis of the role of NO-sulindac in radiosensitising hypoxic PC-3 cells showed that NO-sulindac caused significant radiosensitisation under normoxia, but particularly in hypoxic conditions. As such, NO-NSAIDs show great promise as neoadjuvant, concurrent and adjuvant treatments for patients with hypoxic prostate cancer. The findings of this thesis illustrate several potential novel strategies for treatment of hormone-independent prostate cancer.
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Elgaafary, Menna [Verfasser]. "Pharmacological studies on phytochemicals for the treatment of prostate cancer / Menna Elgaafary." Ulm : Universität Ulm. Medizinische Fakultät, 2016. http://d-nb.info/1081985909/34.
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Ahmed, H. U. "An evaluation of focal therapy in the treatment of localised prostate cancer." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1419862/.
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In this doctoral thesis I am proposing a paradigm shift in the management of men with localised prostate cancer involving destroying areas of prostate cancer alone – so-called focal therapy. By doing so, I propose that side-effects of whole-gland therapies will be reduced whilst maintaining cancer control. I have carried out a phased and structured programme of work to test this hypothesis. First, I review the literature to define the current problem faced by men with localised prostate cancer – namely over-diagnosis and over-treatment with treatment-related side-effects. I demonstrate why multifocality of prostate cancer seems the key impediment to tissue preservation (focal therapy) and why our thinking on multifocality should change. Second, I then tackle how we can accurately localised disease. I evaluate and determine that that using template mapping biopsies is more accurate at localising clinically significant lesions compared to transrectal ultrasound-guided biopsies. Further, I show that histological features of poor prognosis predominantly reside with the index lesion in the presence of multifocal disease. I then evaluate the role of multi-parametric MRI in detecting and ruling-out clinically significant disease using two key and unique datasets of men. I show that the negative predictive value of multi-parametric MRI – the key attribute when proposing to leave parts of the prostate untreated - ranges from 90% to 95% for clinically significant cancer. Third, I evaluate the side-effects and early disease control outcomes of focal therapy within two prospective development studies which are research ethics committee and National Cancer Research Network approved. The Hemi-HIFU study demonstrated that approximately 90% of 20 men treated with hemiablation for unilateral cancer, achieved the trifecta status of pad-free, leak-free continence, erections sufficient for intercourse and cancer control at 12 months. The Focal-HIFU study demonstrated that focal therapy targeted individual lesions rather than one-half of a prostate leads to trifecta outcomes in 84% of 41 men. These results are extraordinary when one considers that trifecta rates after radical therapy are in the order of 50%. My data support the contention that focal therapy has a role in decreasing many of the harms associated with standard whole-gland therapies. This programme of work has now led to a number of multicentre trials testing the reproducibility of these findings with longer follow-up. It has also led to a change in standard practice across a number of international centres. Ultimately, comparative effectiveness research will be necessary to determine the true role of focal therapy in treating localised prostate cancer.
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Brzezinska, Elspeth Anne. "The role of β-catenin in prostate cancer tumourigenesis and treatment resistance." Thesis, University of Glasgow, 2015. http://theses.gla.ac.uk/7019/.
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Prostate cancer is a significant health problem for men in the western world. Of particular concern are patients who present with aggressive, invasive and metastatic disease, and develop lethal castration-resistant prostate cancer (CRPC) following androgen deprivation therapy. The activation of Wnt/β-catenin signalling is a common event in patients with the poorest prognosis, and frequently associated with the loss of PTEN and activation of the PI3K/Akt signalling pathway. However, the molecular basis for the significant impact of these aberrations in prostate cancer remains unclear. By using pre-clinical transgenic in vivo models, we have demonstrated that β-catenin is a potent proto-oncogene that drives prostate cancer tumourigenesis. Concurrent heterozygous loss of Pten exacerbates β-catenin-driven tumour progression and decreases host survival, while tumours are most aggressive when Pten is deleted. By investigating differential gene and protein expression, we have characterised co-operation between β-catenin activation and Pten loss through a complex network of intrinsic and extrinsic molecular events. These drive survival, growth and proliferation signals, and modulate tumour-immune response interactions to evade anti-tumourigenic processes, resulting in aggressive prostate cancer. Furthermore, by examining novel in vivo models of β-catenin-driven CRPC, we have indicated that β-catenin may promote treatment-resistance through androgen receptor (AR) reprogramming. We propose a mechanism for β-catenin-driven CRPC that is independent of classical AR signalling, and mediated through significant upregulation of canonical and non-canonical Wnt pathway components, which may be effectively targeted by Wnt inhibition. In summary, this thesis highlights a number of potential biomarkers and molecular targets that may be exploited to develop new strategies to manage patients with aggressive prostate cancer, to improve prognosis and avoid progression to lethal castration-resistant disease.
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Kachroo, Naveen. "Identification of treatment-specific predictive biomarkers in prostate cancer by transcriptional profiling of archival diagnostic biopsies." Thesis, University of Cambridge, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.707979.
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Skogseth, Haakon R. "Invasive properties of cancer - a treatment target? : In vitro studies in human prostate cancer cell lines." Doctoral thesis, Norwegian University of Science and Technology, Department of Cancer Research and Molecular Medicine, 2007. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-1826.
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Neal, Anthony James. "Optimisation of radiotherapy treatment planning for tumours of the breast, prostate and brain." Thesis, King's College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306922.
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Klaff, Rami. "Disease-Specific Survival in Prostate Cancer Patients : Results from the Scandinavian Prostate Cancer Group (SPCG) Trial No. 5 and Regional Cancer Register Data." Doctoral thesis, Linköpings universitet, Institutionen för klinisk och experimentell medicin, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-132385.
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Introduction Prostate cancer (PCa) is the most common cancer among men in Sweden. The clinical course varies considerably, which makes it difficult to predict the prognosis in the individual case. In order to explore the early as well as the late course of the disease, large study groups and population-based cohorts are necessary. Aims To explore factors that influence the long-term outcome of men with low-risk tumours in a population-based register, to predict the long-term course, and to assess the mortality rate for men with prostate cancer (Paper I) To analyse long-term outcome and to investigate factors associated with long-term survival in patients with metastases to the skeleton (Paper II) To analyse early androgen deprivation treatment (ADT) failure and to define clinical predictors associated with short survival due to early ADT failure in prostate cancer patients with bone metastases (Paper III) To analyse the prognostic significance of the extent of bone metastases in relation to other pretreatment variables in prostate cancer patients, and to explore the impact of bone metastases on quality-of-life (Paper IV) Material and methods The study groups were assembled from The South East Region Prostate Cancer Register (SERPCR), and The Scandinavian Prostate Cancer Group (SPCG) Trial No. 5. In the first study, prognostic factors and long-term disease-specific mortality rates of low-risk prostate cancer patients from the early PSA era were analysed. In the second study, patient-related factors, quality-of-life (QoL) and long-term survival in 915 PCa patients with bone metastases (M1b) under ADT, were analysed. In Study III factors predicting primary failure to respond to ADT were identified. Study IV explored the impact of the extent of bone metastases on survival and QoL for these men. Result and conclusions The long-term disease-specific mortality of low-risk localised PCa is low, but the annual mortality rate gradually increases. This indicates that some tumours slowly develop into lethal cancer, particularly in men 70 years or older and with a PSA level ≥ 4 μg/L. From the SPCG Trial No. 5, a subgroup of patients with M1b disease and favourable set of predictive factors survived more than 10 years under ADT with an acceptable QoL. Independent predictors of long-term survival were identified as performance status (PS) < 2, limited extent of bone metastases, and a PSA level < 231 μg/L at the time of enrolment in the trial. However, four independent clinical predictors of early ADT failure could be defined. Men exhibiting these features should be considered for an alternative treatment. Patient grouping based on three categories of extent of bone metastases related to PS, haemoglobin, and QoL at presentation, as independent predictors of mortality, may provide improved accuracy of prognosis.
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Kou, Tzuyung Doug. "Watchful Waiting Active Surveillance in Prostate Cancer Patients a Population-Based Study Using the SEER-Medicare Linked Database." Cleveland, Ohio : Case Western Reserve University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1207309899.
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Thesis (Ph.D.)--Case Western Reserve University, 2008Title from PDF (viewed on 26 May 2009) Includes abstract Department of Epidemiology and Biostatistics Includes bibliographical references [and appendices] Available online via the OhioLINK ETD Center